title: Oral exposure to acrolein exacerbates atherosclerosis in apoE-null mice.
abstract: BACKGROUND
  Acrolein is a dietary aldehyde that is present in high concentrations in alcoholic beverages and foods including cheese, donuts and coffee. It is also abundant in tobacco smoke, automobile exhaust and industrial waste and is generated in vivo during inflammation and oxidative stress.
  
  
  OBJECTIVE
  The goal of this study was to examine the effects of dietary acrolein on atherosclerosis.
  
  
  METHODS
  Eight-week-old male apoE-null mice were gavage-fed acrolein (2.5mg/kg/day) for 8 weeks. Atherosclerotic lesion formation and composition and plasma lipids and platelet factor 4 (PF4) levels were measured. Effects of acrolein and PF4 on endothelial cell function was measured in vitro.
  
  
  RESULTS
  Acrolein feeding increased the concentration of cholesterol in the plasma. NMR analysis of the lipoproteins showed that acrolein feeding increased the abundance of small and medium VLDL particles. Acrolein feeding also increased atherosclerotic lesion formation in the aortic valve and the aortic arch. Immunohistochemical analysis showed increased macrophage accumulation in the lesions of acrolein-fed mice. Plasma PF4 levels and accumulation of PF4 in atherosclerotic lesions was increased in the acrolein-fed mice. Incubation of endothelial cells with the plasma of acrolein-fed mice augmented transmigration of monocytic cells, which was abolished by anti-PF4 antibody treatment.
  
  
  CONCLUSIONS
  Dietary exposure to acrolein exacerbates atherosclerosis in apoE-null mice. Consumption of foods and beverages rich in unsaturated aldehydes such as acrolein may be a contributing factor to the progression of atherosclerotic lesions.
authors.affiliation: Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202, USA. sanjay@louisville.edu
authors.forename: Sanjay
authors.initials: S
authors.lastname: Srivastava
authors.forename: Srinivas D
authors.initials: SD
authors.lastname: Sithu
authors.forename: Elena
authors.initials: E
authors.lastname: Vladykovskaya
authors.forename: Petra
authors.initials: P
authors.lastname: Haberzettl
authors.forename: David J
authors.initials: DJ
authors.lastname: Hoetker
authors.forename: Maqsood A
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Conklin
authors.forename: Stanley E
authors.initials: SE
authors.lastname: D'Souza
authors.forename: Aruni
authors.initials: A
authors.lastname: Bhatnagar
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000139:chemically induced / Q000473:pathology*; D002784:Cholesterol; D004032:Diet; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010978:Platelet Factor 4 / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D010978:Platelet Factor 4; D000171:Acrolein; D002784:Cholesterol